An enantioselective total synthesis of the antitumor agent anguidine is proposed. Anguidine is a representative member of the trichothecane group of naturally occurring sesquiterpenes produced by imperfect fungi. Several trichothecanes exhibit potent cytotoxic activity and anguidine is currently undergoing clinical trials as a cancer chemotherapeutic agent. Numerous synthetic intermediates will be prepared during the course of this study which will be screened by "in vitro" methods to provide important structure-activity data concerning the onset and optimization of antitumor activity. These results may lead to the synthesis of relatively simple analogs for eventual clinical applications for cancer chemotherapy. The synthetic strategy we propose for the synthesis of anguidine involves four main phases; (1) the preparation of a fully functionalized chiral cyclopentane C-ring (2) stereoselective addition of the A-ring unit (3) intramolecular cyclization to form the central B-ring and (4) subsequent modification of the trichothecane skeleton to provide anguidine 1. The synthetic scheme provides elements of flexibility which will allow synthetic access to other natural trichothecanes and analogs. Our synthetic study will develop methods generally applicable to complex natural product synthesis, including, new applications of microbial reactions in organic synthesis to provide chiral precursors and the use of intramolecular functional group interactions to control relative stereochemistry.